The field of fiber optic (FO) sensors has been subject of extensive research and development and applications of such sensors cover a broad range of parameter measurements such as measurements of physical, biomedical, chemical, biochemical and physiological parameters such as, for example, measurements of oxygen, pH, or carbon dioxide concentration in blood, or measurement of blood glucose and lactate. In comparison, the related art is relatively silent with respect to FO-sensors adapted to measure such blood electrolytes as sodium, potassium, calcium, and chloride, among others. Possible reasons for limited teachings in this area include the fact that the real-time adjustment of levels of these electrolytes in the ill-patient's blood is not as critical to the patient's health management as the real-time adjustment of levels of oxygen, pH, or CO2, for example. as a result, it often suffices to monitor these electrolytes intermittently and not continuously.
FO-optical sensors of the related art (such as, for example, U.S. Pat. Nos. 4,682,895; 5,006,314; 4,974,929; 4,824,789) conventionally include an indicator (dye) such as fluorescent or absorption dye, which interacts with the component to be sensed or measured. Fluorescent dyes, the emissions of which, produced under illumination by light delivered through an optical fiber from an optical source, are affected by the blood constituents or analytes are often incorporated in a semi-permeable polymeric matrix and attached to the optical fiber. The intensity of such fluorescence of the dye relates to the level of an analyte in a sample under test, and therefore can be collected, delivered to a detector, and measured to give an indication of the concentration of the blood constituent. FO-based sensing probes of the related art may include a reflection-based optical path or a fluoremetric indicator system. Discussion of the related art and applications can be also found in “Chemical Sensors Based On Immobilized Indicators And Fiber Optics,” by W. Rudolf Seitz from Fiber Optic Chemical and Biosensors (Otto S. Wolfbeis, vol. I & II, CRC Press, 1991, Boca Raton, Fla., 1991), or “Principles of Fluorescence Spectroscopy” by Joseph R. Lakowicz (Springer, New York, 2006) and “Biomedical Sensors Using Optical Fibers,” A. G. Mignani and F. Balidini, Rep. Prog. Phys., v. 59, 1-28 (1996) and other publications. Various related patents include, to name just a few, U.S. Pat. Nos. 5,124,130; 5,397,411; 5,335,305, and 5,408,999 and the PCT Publication WO 94/10553 disclosing methods and chemical compositions related to a tri-analyte FO biocompatible probe for use in critical care environment. U.S. Pat. No. 4,849,172 disclosing an optical sensor having a gas permeable silicone matrix that contains a high concentration of an optical indicator consisting essentially of a mixture of derivatives of a polynuclear aromatic compound and U.S. Pat. No. 4,857,273 disclosing a sensor including a means for enhancement of a light signal; a U.S. Pat. No. 4,861,727 describing a luminescent oxygen sensor using a lanthanide complex; a U.S. Pat. No. 4,558,014 disclosing an assay apparatus employing fluorescence effects; and U.S. Patent Application Publication No. 2008/0199360 teaching methods of making fluorescence oxygen sensor based on sol-gel materials incorporating fluorescent dyes in such a relatively unstable fashion allowing the dyes to be washed out over time the sensor is being exploited. The use of sensors discussed in these patent documents is restricted to non-clinical applications where size or biocompatibility issues are not critical.
One of the known applications of FO-sensors related to survival of tissue cells, which rely on adequate supply of oxygen to the mitochondria within the tissue cells. The significance of partial pressure of brain tissue oxygen measurements demonstrating cerebral hypoxia, ischemia, or both is very well known. For example, continuous brain-tissue monitoring involving measurements of oxygen delivery and identification of cerebral hypoxia and ischemia in patients with brain injury, aneurysmal subarachnoid hemorrhage, malignant stroke, or other patients at risk for secondary brain injury has been described in related art employing Fiber Optic-sensors the operation of which is based on measurements of either intensity or life-time decay of generated fluorescent light. The decay life-time of fluorescence, for example, is inversely proportional to the concentration of oxygen and relates to an absolute value of pO2 in mm Hg. U.S. Patent Application Publication No. 2009/0075321 discloses a fiber optic sensor for measuring oxygen concentration in tissue and comprising an optical glass fiber passing through a gas-isolation collar into a cavity filled with a polymer and a fluorescent dye material. Fluorescent indicator material used in this invention uses platinum complex of substituted porphyrines. A related configuration using a phosphorescent based solution, encapsulated with an oxygen permeable membrane, which produces oxygen-quenchable phosphorescence, is reported in U.S. Patent Application Publication No. 2009/0216097. An example of a fluoremetric fiber optic sensor is described in U.S. Patent Application Publication No. 2009/0075321, discussing the employment of optical fiber extending longitudinally into an elongated cavity that is defined by a surrounding wall and has an open end remote from that through which the optical fiber passes. Each of the above mentioned patent documents is incorporated herein by reference in its entirety.
Shortcomings of conventional fiber-optic based biological sensors prevent the existing designs from assuring the optimized operation in field conditions. Three common types of design are representative in this respect. For example, the use of bent upon itself fiber optic (for example, looped over a mandrel or spoke, with radius comparable to that of the optical fiber), the input and output segments of which are both contained within the body of the probe not only significantly decreases the efficiency of light transmission due to light leaks at a tight-radius bend but also sets a low limit on the density of FO-elements within the probe. The use of shallow cavities, in the fiber optic, that graze the fiber optic core limit the degree of interaction between the excitation light and the analyte and thus does not allow to increase the sensor's sensitivity above a certain level. Yet in another common implementation, the placement of the analyte-sensitive material adjacent to the tip of the fiber optic that is being inserted into a biological tissue makes the sensing probe vulnerable to being disrupted and mechanically disintegrated.
It is an aim of fiber optic sensor/probe development to combine more than one sensor in a single probe so that a patient is not overtaxed with various probes introduced in his or her arteries or skin tissues. While the related literature offers a variety of designs attempting to achieve this goal, the problem is far from being solved and there remains a need in a multi-sensor probe having an optimized density of fiber-optic sensors that perform continuous, real-time, and temperature and pressure-normalized determination of physiological elements such as analytes and/or physical parameters describing a biological environment (such as a patient under test) and that have optimized sensitivity. The present invention addresses the operational shortcoming of the related art and offers a probe having optimized density of fiber-optic sensors.